My coworkers and I study adult stem cells that live in the bone marrow. Some of these cells give rise to red and white blood cells and are called hematopoietic stem cells (HSCs). Others give rise to bone, cartilage, and fat and are called bone marrow stromal cells (BMSCs). We found that these different populations are connected to each other and can and do regulate each others' function. We study how bone marrow stromal cells, (also known as mesenchymal stem cells or MSCs) regulate cells of the immune system. We use mice to study effects on the whole system and follow up with using human cells in tissue culture to examine the effect of MSCs. We look at a variety of cells that they are in close contact with in the bone marrow, such as red cells and their progeny as well as the white cell lineage (immune cells). These studies help clinicians to find out how they can use MSCs most efficiently to treat patients with a variety of immune related and inflammatory diseases. To optimize their use we are also trying to find ways to increase the therapeutical potential of MSCs by pretreating them with growth factors or changing their environment before their infusion in patients. Since these cells have now been used in the clinics in immune-related diseases, any such way that increase their immune regulatory potential might mean that less cells could be used with more efficiency to the benefit of the patients. We also study the function of BMSCs in red cell production. We are using in vitro cultures to see the interaction between human BMSCs and blood stem cells (HSCs) isolated from healthy volunteers. We are looking for agents that the BMSC can release to regulate the number and class of blood cells that are made in the bone marrow. Since iron is an essential building block of red cells, we study how iron storage and release are regulated within and outside of the bone marrow. Finding ways to induce red cell production through stimulating the supportive stromal cells (MSCs) could help people with anemia due to disease or chemotherapy.